Support The World's Smartest Network

Help the New York Academy of Sciences bring late-breaking scientific information about the COVID-19 pandemic to global audiences. Please make a tax-deductible gift today.

This site uses cookies.
Learn more.


This website uses cookies. Some of the cookies we use are essential for parts of the website to operate while others offer you a better browsing experience. You give us your permission to use cookies, by continuing to use our website after you have received the cookie notification. To find out more about cookies on this website and how to change your cookie settings, see our Privacy policy and Terms of Use.

We encourage you to learn more about cookies on our site in our Privacy policy and Terms of Use.

Sulfur in Chemistry and Biology

Sulfur in Chemistry and Biology

Wednesday, October 4, 2006

The New York Academy of Sciences

Presented By


Organizer: Thomas Leyh, Albert Einstein College of Medicine

Speakers: Thomas Leyh, Albert Einstein College of Medicine; Tadhg Begley, Cornell University, Ithaca, NY; Kate Carroll, University of Michigan, Ann Arbor, Meihao Sun, Albert Einstein College of Medicine


The Catalytic Manipulation of Sulfate: Thomas Leyh

The unfavorable energetics of the sulfate activating chemistry presents a formidable catalytic challenge to the enzymes charged with timely provision of this essential nutrient. Nature has responded to this challenge with a suite of remarkable molecular inventions, which will be central to our discussion. Once activated, the sulfuryl-moiety can be transferred enzymatically to cellular recipients in reactions that are used widely to regulate metabolism. The first transition-state structure of an enzyme-catalyzed, sulfuryl-transfer reaction was determined recently and will be considered in the context of the enzyme that binds tightly to it – the human estrogen sulfotransferase.

Thiamin: A Simple Vitamin with a Complex Biosynthetic Pathway: Tadhg Begley

Thiamin pyrophosphate is an essential cofactor in all-living systems and consists of a pyrimidine covalently linked to a thiazole. The biosynthesis of thiamin is complex and different from any of the characterized chemical or biochemical routes to these heterocycles. This lecture will cover the current status of mechanistic and structural studies on the thiazole biosynthetic enzymes as well as related studies on cysteine and thioquinolobactin biosynthesis. The carbon sulfur bond forming steps in each case will be described.

Reducing the mysteries of sulfur metabolism in Mycobacterium tuberculosis: Kate Carroll

Mycobacterium tuberculosis (M. tb) is the most lethal single infectious agent, accounting for an estimated 3 million deaths per year worldwide. In addition, the number of persons infected with multidrug resistant (MDR) strains of M. tb continues to grow and 79 percent of these cases now show resistance to three or more drugs. These numbers underscore the need for new target identification and antibiotics to address the growing problem of MDR M. tb. To complete its life cycle, M. tb must survive within the nutrient-poor and oxidizing environment of the host macrophage. NO and superoxide are produced in response to M. tb infection and it is likely that the bacterium has a mechanism of protection against these reactive oxidants. Products of the reductive sulfate assimilation pathway, such as the abundant antioxidant mycothiol, are excellent candidates for this function. We are currently investigating the mechanism of APS reductase, the enzyme that catalyzes the first committed step of reductive sulfate assimilation and the role that sulfur-containing metabolites play in the replication and persistence of Mycobacteria. The biosynthetic machinery associated with critical metabolites may offer new targets for anti-tuberculosis therapy.

Half-of-Sites Reactivity of Human Estrogen Sulfotransferase: Meihao Sun

Estradiol, the principal and most active circulating estrogen, plays an important role in human breast carcinogenesis. Its hormonal activity can be decreased by conjugation to sulfate, which is catalyzed by the homodimeric enzyme estrogen sulfotransferase (EST). A pre-steady state study on EST showed that there is a burst phase (amplitude equals half of the enzyme active sites) in the formation of E2S followed by steady state turnover. Analysis of pre-steady state data and isotope trapping experiments suggests that the ternary central complex equilibrium favors enzyme-bound product formation. In addition, the observation that rate of product Michaelis complex formation was much faster than that of later steps implies that the magnitude of the burst reflects the active enzyme concentration. Taken together, these results demonstrate that EST is a half-of-sites reactivity enzy